Jpn. J. Pharmacol. 71 (1), 39-49 (1996)

ME3221, a Surmountable Angiotensin AT1-Receptor Antagonist, Prevents Hypertensive Complications in Aged Stroke-Prone Spontaneously Hypertensive Rats

Jun Nagura, Chen Hui, Mikio Yamamoto, Sumie Yasuda, Mitsuhiro Abe, Mitsugu Hachisu and Fukio Konno

Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222, Japan

Abstract: The protective effects of ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'- biphenyl-4-yl]methoxy] pyridine, on aged (32-week-old) stroke-prone spontaneously hypertensive rats (SHRSP) were studied following long-term (for 8 months) oral administration. At a dose of 10 mg/kg/day, ME3221 suppressed the mortality and the hypertensive complications observed in control SHRSP: cerebral apoplexy (hemorrhage, and spongeform and malacia in the cerebral cortex), increased proteinuria, and total N-acetyl-beta-D-glucosaminidase activity, and cardiac hypertrophy and pleural effusion. The protective activity of ME3221, a surmountable angiotensin AT1-receptor antagonist, was comparable to losartan, an insurmountable AT1-antagonist, and also to enalapril, an angiotensin-converting enzyme inhibitor. In addition, ME3221 reduced the systolic blood pressure more effectively than the two reference drugs.

Keywords: ME3221, Angiotensin AT1-receptor antagonist, Stroke-prone spontaneously hypertensive rat

Copyright© The Japanese Pharmacological Society 1996

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